The long term objective is to determine common mechanisms regulating biological mineralization in order to provide relevant new information concerning normal and pathological mineralized tissue development in humans. We propose to study the ultrastructure of normal and pharmacologically altered tooth buds in lower vertebrate species which temporally separate matrix and primary mineralization stages of development. We will investigate specific teleost and elasmabranch species which concentrate low environmental levels of fluoride into their enamels in order to better understand the effects fluoride has on mineralizing tissues. Specifically, the relative protein contributions that cichlid and skate dental epithelial cells and odontoblasts make to the unmineralized matrix components will be determined by autoradiographic, immunological, and pharmacological administration of colchicine, fluoride, and L azetidine carboxylic acid. The ion permeability and protein resorption functions of odontogenic cells regulating matrix mineralization will be determined by lanthanum nitrate and horseradish peroxidase tracer methodology and phosphatase activity. The effect fluoride has on the secretory, resorptive, and ion regulatory functions of odontogenic cells will also be investigated. The structural similarity of the matrix mineral relationships between lower vertebrate and mammalian tooth buds will be established by high resolution transmission electron microscopy of preferentially extracted matrix components and unextracted matrix components from normal and experimentally altered tooth buds. The proposed studies will provide new structural and functional information concerning the regulatory mechanisms involved in the secretion and mineralization of collagenous and non-collagenous matrix proteins.